Optimum time to assess complete clinical response (CR) following chemoradiation (CRT) using mitomycin (MMC) or cisplatin (CisP), with or without maintenance CisP/5FU in squamous cell carcinoma of the anus: Results of ACT II

In the ACT I trial, relapse-free survival was improved with chemoradiotherapy compared to radiotherapy alone, but the complete response (CR) rate at 6 weeks was similar (39% CRT, 30% RT alone; p=0.08).

Most studies assess CR between 6 and 12 weeks following completion of CRT.

The preliminary results of ACT II were presented at ASCO 2009. With a median follow-up of 3 years, there was no difference in CR rates between MMC and Cisplatin with or without maintenance chemotherapy.

This ACT II study investigates the association between observation of CR at 3 different time-points and progression-free and overall survival (PFS, OS), to determine the optimal time to assess this early endpoint.

Materials and Methods

This is a multicenter, randomized factorial trial that enrolled patients between June 2001- December 2008 and compared Cisplatin (60mg/m2 on d1+ d29) versus MMC (12mg/m2 on d1 only) when combined with 5-FU (1000mg/m2 d1-4 +d29-32) concurrent chemoradiotherapy, and two cycles of maintenance chemotherapy versus no maintenance.

Radiation therapy was delivered with 3D conformal radiation therapy with parallel-opposed fields. The whole pelvis was treated to 3060 cGy (in 180 cGy daily fractions) with a cone-down to the primary tumor to a total dose of 5040 cGy).

Patients were excluded if assessment was not done/ missing at one or more time points.

CR (complete absence of tumor and node negative) was assessed by digital rectal exam or exam under anesthesia at

11 weeks (or 4 weeks after end of CRT)

18 weeks (10-11 weeks after CRT and pre-maintenance)

26 weeks (19 weeks after CRT and 4 weeks post-maintenance)

At 26 weeks, response assessment also included a CT of the abdomen/pelvis and chest X-ray

Clinical Implications

Because many patients who did not achieve complete response at 11 weeks had complete regression of their tumor at 26 weeks, response assessment at 26 weeks will prevent many patients from undergoing unnecessary salvage surgery

It is important to note that while response assessment at 26 weeks benefits late responders to therapy, earlier response assessment at 11-18 weeks is still necessary to identify patients with progressive disease.